The influence of protein solubilisation, conformation and size on the burst release from poly(lactide-co-glycolide) microspheres.

Encapsulation of proteins in poly(lactide-co-glycolide) microspheres via emulsion is known to cause insoluble protein aggregates. Following protein emulsification and encapsulation in PLGA microspheres, we used circular dichroism to show that the recoverable soluble protein fraction also suffers subtle conformational changes. For a panel of proteins selected on the basis of molecular size and structural class, conformational stability measured by chemical denaturation was not indicative of stability during emulsion-encapsulation. Partial loss of structure was observed for alpha-helical proteins released from freeze-dried microspheres in aqueous buffer, with dramatic loss of structure for a beta-sandwich protein. The addition of sucrose (a lyoprotectant) did not prevent the loss of protein conformation upon encapsulation. Therefore, the conformational changes seen for the released soluble protein fraction originates during emulsification rather than microsphere freeze-drying. Analysis of the burst release for all proteins in buffer containing denaturant or surfactant showed that the degree of protein solubilisation was the dominant factor in determining the initial rate and extent of release. Our data for protein release into increasing concentrations of denaturing buffer suggest that the emulsion-denatured protein fraction remains insoluble; this fraction may represent the protein loss encountered upon comparison of protein encapsulated versus protein released.     

Utility of the PFA-100 as a screening test of platelet function: an audit of haemostasis laboratories in Australia and New Zealand.

The PFA-100 is a relatively new laboratory instrument, first described in 1995. There have since been numerous studies assessing its utility as a screening tool for platelet dysfunction and/or von Willebrand's disease (VWD). The PFA-100 displays variable sensitivity to different types of platelet disorders, as well as to antiplatelet medication (e.g. aspirin), with similar caveats for monitoring of primary haemostasis-promoting therapies in platelet dysfunction. There is therefore considerable uncertainty regarding its utility within this context, and we have accordingly performed an audit of usage among participants of the Royal College of Pathologists of Australasia Quality Assurance Program. Of 105 laboratories surveyed, 40 responded that they performed platelet function testing, with 26 (65%) further indicating they utilized the PFA-100. We report a wide variety of laboratory usage among these users, including numbers of tests performed [annual median (range) = 270 (15-6000)], sources of requests (clinical sources and localities), testing criteria and follow-up action. Most tests were completed within 4 h of collection, as recommended by the manufacturer, and most tests were performed as a replacement, or as a preliminary screen of platelet function (i.e. classical aggregation). Most abnormal findings, however, were attributed to antiplatelet medication such as aspirin.     

Cross-calibration of dual-energy X-ray densitometers for a large, multi-center genetic study of osteoporosis

Osteoporosis is a common disease with a strong genetic component characterized by reduced bone mass and an increased risk of fragility fractures. Bone mineral density (BMD) is the most important determinant of osteoporotic fracture risk, but the genes responsible for BMD regulation and fracture are incompletely defined. To enable multi-center studies to examine the genetic influences on BMD there is a requirement to standardize measurements across different manufacturers of bone densitometers, different versions of machines and different normative ranges. This paper describes a method developed to allow near-identical subjects with low age-adjusted BMD (based on Z-scores) to be recruited in 17 centers using 27 different densitometers. Cross-calibration was based on measurements using a European spine phantom circulated to all centers and measured ten times on each individual machine. From theses values an individual exponential curve, based on nominal versus observed BMD, was derived for each machine. As expected, there were large and significant variations in nominal BMD values, not only between scanners from different manufacturers but also between different versions of scanners from the same manufacturer. Hologic scanners tended to underestimate the nominal BMD, while Lunar scanners overestimated the value. Norland scanners gave mixed values over estimating BMD at the lower nominal value (0.5 g/cm²) while underestimating the value at the higher value (1.5 g/cm²). The validity of the exponential equations was tested using hip and spine measurements on 991 non-proband women from a familial osteoporosis study (FAMOS). After cross-calibration there was a considerable reduction in variation between machines. This observation, coupled with the absence of a similar reduction in variation attributable to a linear regression on age, demonstrated the validity of the cross-calibration approach. Use of the cross-calibration curves along with a standard normative range (in the case of this study, the Hologic normative range) allowed age-specific Z-scores to be used as an inclusion criterion in this genetic study, a method that will be useful for other trials where age-specific BMD inclusion criteria are required.     

SNAP-II predicts mortality among infants with congenital diaphragmatic hernia.

OBJECTIVE: Outcomes analysis in congenital diaphragmatic hernia (CDH) requires a validated risk-adjustment tool. The purpose of this study was to use the Canadian Neonatal Network (CNN) database to validate the Score for Neonatal Acute Physiology, Version II (SNAP-II) for prediction of mortality among CDH infants admitted to a neonatal intensive care unit (NICU), and to compare this to the predictive equation recently developed by the Congenital Diaphragmatic Hernia Study Group (CDHSG). STUDY DESIGN: Infants with CDH in the CNN database were identified. Bivariate and multivariable logistic regression models were used to identify risk factors predictive of mortality. Model predictive performance and calibration were assessed using the area under the receiver operator characteristic curve and the technique of Hosmer-Lemeshow, respectively, and compared with the CDHSG predictive equation. RESULTS: There were 88 patients with CDH among 19,507 admissions to CNN hospitals. The mortality rate among CDH patients surviving to NICU admission was 17%, and 12.5% received extracorporeal membrane oxygenation therapy. Gestational age and admission SNAP-II score predicted mortality. Model predictive performance and calibration were optimized with these variables combined. The CDHSG equation was equally predictive of mortality, but was only marginally calibrated. CONCLUSIONS: SNAP-II is highly predictive of mortality among patients with CDH, and can be used to risk-adjust these patients.     

Iowa's High School High Tech Goes to College Program: Preparing Students with Mild Disabilities for Careers in Technology

This paper describes an innovative approach to preparing high school students with mild disabilities for challenging careers in high tech industries, called High School High Tech (HSHT). Iowa's HSHT Goes to College program has three central elements, each of which is discussed in this paper: High School Preparation—assisting students in identifying a suitable high tech career goal; Higher Education Preparation and Supports—assisting students in selecting college/training programs that match their career goal, and in successfully completing their postsecondary programs; Workforce Entry Assistance—linking students with employers and launching their high tech careers. The paper concludes with a presentation of outcomes to date and recommendations for program enhancements. The information presented here is intended to assist education and rehabilitation professionals interested in establishing similar efforts across the nation.     

A historical overview of spirituality in nursing.

The following article is an attempt to encapsulate an historical overview of spirituality in nursing. Despite a plethora of information relative to spirituality in nursing, the decision was to do an eclectic overview that was not reflective of any one spiritual/religious group. The authors at times found this goal difficult when writing about the Pre-Christian and Christian eras. Most of the major religions have their own perspective on the concept of spirituality, and historical personalities recorded maybe reflective of that particular religion. Another factor that impacted on the writing of this article was the concept that spirituality was not always linked specifically to religion. Spirituality was an experiential component of the wonders of nature and life, a domain that the authors took into account but did not expound upon. Finally the authors realized that spirituality has almost always been an aspect of African-American life and certainly of those in nursing. To this end the authors realize that there is a need for more research in this area.